2HDR: Ampc Beta-lactamase In Complex With 4-amino-3-hydroxybenzoic Acid

Citation:
Abstract
Fragment-based screens test multiple low-molecular weight molecules for binding to a target. Fragments often bind with low affinities but typically have better ligand efficiencies (DeltaG(bind)/heavy atom count) than traditional screening hits. This efficiency, combined with accompanying atomic-resolution structures, has made fragments popular starting points for drug discovery programs. Fragment-based design adopts a constructive strategy: affinity is enhanced either by cycles of functional-group addition or by joining two independent fragments together. The final inhibitor is expected to adopt the same geometry as the original fragment hit. Here we consider whether the inverse, deconstructive logic also applies--can one always parse a higher-affinity inhibitor into fragments that recapitulate the binding geometry of the larger molecule? Cocrystal structures of fragments deconstructed from a known beta-lactamase inhibitor suggest that this is not always the case.
PDB ID: 2HDRDownload
MMDB ID: 42839
PDB Deposition Date: 2006/6/20
Updated in MMDB: 2006/12
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 2HDR: monomeric; determined by author
Molecular Components in 2HDR
Label Count Molecule
Protein (1 molecule)
1
Beta-lactamase(Gene symbol: ampC)
Molecule annotation
Chemicals (10 molecules)
1
1
2
9
* Click molecule labels to explore molecular sequence information.

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